Andrographolide, Bioactive Compounds of Andrographis paniculata as Alternative Therapeutic for Cancer

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Published: Aug 31, 2023
Keywords:
Andrographis paniculata Andrographolide Cancer

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Kanoknetr Suksen
Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Rama VI Road, Ratchathewi District, Bangkok 10400, Thailand
Nittaya Boonmuen
Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Rama VI Road, Ratchathewi District, Bangkok 10400, Thailand
Rungnapha Saeeng
Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand
Parunkul Tungsukruthai
Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand
Noel Pabalan
Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand
Phuntila Tharabenjasin
Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand

Abstract

Introduction and Objective: Herbs have served as medicine throughout human history. Andrographis paniculata with bioactive constituents, diterpene lactone andrographolide (AG), has been shown to have several important biological activities, including antioxidant, anti-inflammatory, immunomodulatory, antiseptic, antimicrobial, and cytotoxic effects. However, there was no previous review focusing on their promising agent in cancer treatment including underpinning mechanism. The present review highlights the scientifically pharmacological potential of AG as anti-cancer activity.


 


Methods: A number of databases (PubMed, Science-Direct, Springer, ACS, NIH, GOOGLE,


MEDLINE, SCOPUS, ATLANTICS and WEB OF SCIENCE) were used to search for the cytotoxic and anticancer effects of AG in pre-clinical and clinical studies. Among systematic screening of 1,455 literature articles, 52 were proposed underlying mechanism of anticancer effect, which were included in this review.


 


Results: Cultured cell lines are attributable to the most part of database followed by in vivo models using rodents. We describe possible underlying mechanism of AG as a natural anticancer agent on almost all types of cell lines involving oxidative stress-induced cell death, cell cycle arrest, anti-inflammatory and immune system mediated effects, apoptosis, necrosis, autophagy, inhibition of cell adhesion, proliferation, migration, metastasis and invasion, and anti-angiogenic effects.


 


Discussion: Our current work sheds some light on the most importance of bioactive constituents, AG, from Andrographis paniculata on anticancer and antitumor activity. By using the main bioactive component, the concentrations or dose of AG was precisely controlled. Regarding the studied limitation, most of the findings cited in this review are mainly based on in vitro and animal studies. More experiments are required to systematically elucidate the physiological significance of AG in human under neuroendocrine regulation.


 


Conclusion and recommendation: Based on our review, AG represents a potential option and could be used as promising candidate for the complementary and alternative medicines for the treatment of cancer in the future.

Article Details

Issue
Vol. 21 No. 2 (2023): May - August 2023
Section
Review Article
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

References

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.

National Cancer Institute. Department of Medical Service. Ministry of Public Health [Internet]. 2013-2017. [cited 2023 Jan 12]; Available from: https://www.nci.go.th/th/cancer_record/cancer_rec1.html (in Thai)

Klein CA. Cancer progression and the invisible phase of metastatic colonization. Nat Rev Cancer. 2020;20(11):681-94.

Mora DC, Kristoffersen AE, Overvåg G, Jong MC, Mentink M, Liu J, Stub T. Safety of Complementary and Alternative Medicine (CAM) treatment among children and young adults who suffer from adverse effects of conventional cancer treatment: A systematic review. Integr Cancer Ther. 2022;21:1-22.

Mishra SK, Tripathi S, Shukla A, Oh SH, Kim HM. Andrographolide and analogues in cancer prevention. Front Biosci (Elite Ed). 2015;7(2):255-66.

Hossain MS, Urbi Z, Sule A, Rahman KMH. Andrographis paniculata (Burm. f.) Wall. ex Nees: A review of ethnobotany, phytochemistry, and pharmacology. ScientificWorldJournal. 2014:274905.

Vetvicka V, Vannucci L. Biological properties of andrographolide, an active ingredient of Andrographis paniculata: a narrative review. Ann Transl Med. 2021;9(14):1186.

Dai Y, Chen SR, Chai L, Zhao J, Wang Y, Wang Y. Overview of pharmacological activities of Andrographis paniculata and its major compound andrographolide. Crit Rev Food Sci Nutr. 2019;59(sup1):S17-29.

Chao WW, Lin BF. Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian). Chin Med. 2010;5:17.

Chakravarti RN, Chakravarti D. Andrographolide, the active constituent of Andrographis paniculata Nees; a preliminary communication. Ind Med Gaz. 1951;86(3):96-7.

Mishra SK, Sangwan NS, Sangwan RS. Andrographis paniculata (Kalmegh): A review. Phcog Rev. 2007;1:283-98.

Islam MT, Ali ES, Uddin SJ, Islam MA, Shaw S, Khan IN, Saravi SSS, Ahmad S, Rehman S, Gupta VK, Găman M, Găman AM, Yele S, Das AK, Castro E Sousa JM, Moura Dantas SMM, Rolim SML, Carvalho Melo-Cavalcante AA, Mubarak MS, Yarla NS, Shilpi JA, Mishra SK, Atanasov AG, Kamal MA. Andrographolide, a diterpene lactone from Andrographis paniculata and its therapeutic promises in cancer. Cancer Lett. 2018;420:129-45.

Islam MT. Andrographolide, an up-coming multi-edged plant-derived sword in cancers!. Asian J Ethnopharmacol Med Foods. 2016;5:1-3.

Lim JCW, Chan TK, Ng DS, Sagineedu SR, Stanslas J, Wong WSF. Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer. Clin Exp Pharmacol Physiol. 2021;39(3):300-10.

Mishra SK, Tripathi S, Shukla A, Oh SH, Kim HM. Andrographolide and analogues in cancer prevention. Frontiers in Biosci. (Elite edition). 2015;7:255-66.

Yang S, Evens AM, Prachand S, Singh AT, Bhalla S, David K, Gordon LI, Mitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone andrographolide, the active component of Andrographis paniculata. Clin Canc Res. 2010);16(19):4755-68.

Banerjee B, Chattopadhyay S, Choudhuri T, Bera R, Kumar S, Chakraborty B, Mukherjee SK. Cytotoxicity and cell cycle arrest induced by andrographolide lead to programmed cell death of MDA-MB-231 breast cancer cell line. J Biomed Sci. 2016;23:40.

Lu H, Zhang XY, Wang YQ, Zheng XL, Yin Z, Xing WM, Zhang Q. Andrographolide sodium bisulfate-induced apoptosis and autophagy in human proximal tubular endothelial cells is a ROS-mediated pathway. Environ Toxicol Pharmacol. 2014;37(2):718-28.

Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R. Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata. J Exp Therapeut Oncol. 2003;3(3):147-58.

Cheung HY, Cheung SH, Li J, Cheung CS, Lai WP, Fong WF, Leung FM, Andrographolide isolated from Andrographis paniculata induces cell cycle arrest and mitochondrial-mediated apoptosis in human leukemic HL-60 cells. Planta Med. 2005;71(12):1106-11.

Wong CC, Lim SH, Sagineedu SR, Lajis NH, Stanslas J. SRJ09, a promising anticancer drug lead: elucidation of mechanisms of antiproliferative and apoptogenic effects and assessment of in vivo antitumor efficacy. Pharmacol Res. 2016;107:66-78.

Shen, Liu TY, Xu C, Ji LL, Wang ZT. Andrographolide inhibits hepatoma cells growth and affects the expression of cell cycle related proteins. Yao Xue Xue Bao. 2009;44(9):973-9.

Yan J, Chen Y, He C, Yang ZZ, Lu C, Chen XS. Andrographolide induces cell cycle arrest and apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes. Cell Biol Toxicol. 2012;28(1):47-56.

Roy P, Das S, Mondal A, Chatterji U, Mukherjee A. Nanoparticle engineering enhances anticancer efficacy of andrographolide in MCF-7 cells and mice bearing EAC. Curr Pharm Biotechnol. 2012;13(15):2669-81.

Kumar S, Patil HS, Sharma P, Kumar D, Dasari S, Puranik VG, Thulasiram HV, Kundu GC. Andrographolide inhibits osteopontin expression and breast tumor growth through down regulation of PI3 kinase/Akt signaling pathway. Curr Mol Med. 2012;12(8):952-66.

Zhang QQ, Zhou DL, Ding Y, Liu HY, Lei Y, Fang HY, Gu QL, He XD, Qi CL, Yang Y, Lan T, Li JC, Gong P, Wu XY, Yang X, Li WD, Wang LJ. Andrographolide inhibits melanoma tumor growth by inactivating the TLR4/ NF-kappaB signaling pathway. Melanoma Res. 2014;24(6):545-55.

Zhu YY, Yu G, Zhang Y, Xu Z, Wang YQ, Yan GR, He QY. A novel andrographolide derivative AL-1 exerts its cytotoxicity on K562 cells through a ROS-dependent mechanism. Proteomics. 2013;13(1):169-78.

Yuan H, Sun B, Gao F, Lan M. Synergistic anticancer effects of andrographolide and paclitaxel against A549 NSCLC cells. Pharm Biol. 2016;54(11):2629-35.

Sheeja K, Guruvayoorappan C, Kuttan G. Antiangiogenic activity of Andrographis paniculata extract and andrographolide. Int Immunopharmacol. 2007;7(2):211-21.

Sheeja K, Kuttan G. Activation of cytotoxic T lymphocyte responses and attenuation of tumor growth in vivo by Andrographis paniculata extract and andrographolide. Immunopharmacol Immunotoxicol. 2007;29(1):81-93.

Chun JY, Tummala R, Nadiminty N, Lou W, Liu C, Yang J, Evans CP, Zhou Q, Gao AC. Andrographolide, an herbal medicine, inhibits interleukin- 6 expression and suppresses prostate cancer cell growth. Genes Cancer. 2010;1(8):868-76.

Guo W, Sun Y, Liu W, Wu X, Guo L, Cai P, Wu X, Wu X, Shen Y, Shu Y, Gu Y, Xu Q. Small molecule-driven mitophagy mediated NLRP3 inflammasome inhibition is responsible for the prevention of colitis-associated cancer. Autophagy. 2014;10(6):972-85.

Guo H, Zhang Z, Su Z, Sun C, Zhang X, Zhao X, Lai X, Su Z, Li Y, Zhan JY. Enhanced anti-tumor activity and reduced toxicity by combination andrographolide and bleomycin in ascitic tumor-bearing mice. Eur J Pharmacol. 2016;776:52-63.

Gong C, Ni Z, Yao C, Zhu X, Ni L, Wang L, Zhu S. A high-throughput assay for screening of natural products that enhanced tumoricidal activity of NK cells. Biol Proced Online. 2015;17:12.

Tzeng YM, Lee YC, Cheng WT, Shih HN, Wang HC, Rao YK, Lee MJ. Effects of andrographolide and 14-deoxy-11,12-didehydroandrographolide on cultured primary astrocytes and PC12 cells. Life Sci. 2012;90(7-8):257-66.

Kim TG, Hwi KK, Hung CS. Morphological and biochemical changes of andrographolide-induced cell death in human prostatic adenocarcinoma PC-3 cells. In Vivo. 2005;19(3):551-7.

Zhou J, Zhang S, Ong CN, Shen HM. Critical role of pro-apoptotic Bcl-2 family members in andrographolide-induced apoptosis in human cancer cells. Biochem Pharmacol. 2006;72:132-44.

Lu H, Zhang XY, Wang YQ, Zheng XL, Yin Z, Xing WM, Zhang Q. Andrographolide sodium bisulfate-induced apoptosis and autophagy in human proximal tubular endothelial cells is a ROS-mediated pathway. Environ Toxicol Pharmacol. 2014;37(2):718-28.

Xu J, Xue T, Bao Y, Wang DH, Ma BL, Yin CY, Yang GH, Ren G, Lan LJ, Wang JQ, Zhang XL, Zhao YQ. Positive therapy of andrographolide in vocal fold leukoplakia. Am J Otolaryngol. 2014;35(2):77-84.

Sukardiman H, Sismindari AW, Zaini NC. Apoptosis inducing effect of andrographolide on TD-47 human breast cancer cell line. Afr J Tradit Complement Altern Med. 2007;4(3):345-51.

Yang L, Wu D, Luo K, Wu S, Wu P. Andrographolide enhances 5- fluorouracil-induced apoptosis via caspase-8-dependent mitochondrial pathway involving p53 participation in hepatocellular carcinoma (SMMC-7721) cells. Cancer Lett. 2009;276(2):180-8.

Yunos NM, Mutalip SS, Jauri MH, Yu JQ, Huq F. Anti-proliferative and pro-apoptotic effects from sequenced combinations of andrographolide and cisplatin on ovarian cancer cell lines. Anticancer Res. 2013;33(10):4365-71.

Pratheeshkumar P, Sheeja K, Kuttan G. Andrographolide induces apoptosis in B16F-10 melanoma cells by inhibiting NF-kappaB-mediated bcl-2 activation and modulating p53-induced caspase-3 gene expression. Immunopharmacol Immunotoxicol. 2012;34(1):143-51.

Li J, Cheung HY, Zhang Z, Chan GK, Fong WF. Andrographolide induces cell cycle arrest at G2/M phase and cell death in HepG2 cells via alteration of reactive oxygen species. Eur J Pharmacol. 2007;568(1-3):31-44.

Yang EJ, Song KS. Andrographolide, a major component of Andrographis paniculata leaves, has the neuroprotective effects on glutamate-induced HT22 cell death. J Funct Foods. 2014;9:162-72.

Zhai Z, Qu X, Yan W, Li H, Liu G, Liu X, Tang T, Qin A, Dai K. Andrographolide prevents human breast cancer-induced osteoclastic bone loss via attenuated RANKL signaling. Breast Cancer Res Treat. 2014;144(1):33-45.

Kumar D, Das B, Sen R, Kundu P, Manna A, Sarkar A, Chowdhury C, Chatterjee M, Das P. Andrographolide analogue induces apoptosis and autophagy mediated cell death in U937 cells by inhibition of PI3K/akt/mTOR pathway. PLoS One. 2015;10(10):e0139657.

Sharifuddin Y, Parry EM, Parry JM. The genotoxicity and cytotoxicity assessments of andrographolide in vitro. Food Chem Toxicol. 2012;50(5):1393-8.

Kumar D, Das B, Sen R, Kundu P, Manna A, Sarkar A, Chowdhury C, Chatterjee M, Das P. Andrographolide analogue induces apoptosis and autophagy mediated cell death in U937 cells by inhibition of PI3K/akt/mTOR pathway, PLoS One. 2015;10:e0139657.

Hsieh MJ, Lin CW, Chiou HL, Yang SF, Chen MK. Dehydroandrographolide, an iNOS inhibitor, extracted from Andrographis paniculata (Burm.f.) Nees, induces autophagy in human oral cancer cells. Oncotarget. 2015;6(31):30831-49.

Bhummaphan N. Induction of cholangiocarcinoma cells apoptosis by an andrographolide analog. Scientific Research and Essays. 2013;8(1):26-31.

Lin HC, Su SL, Lu CY, Lin AH, Lin WC, Liu CS, Yang YC, Wang HM, Lii CK, Chen HW. Andrographolide inhibits hypoxia-induced HIF-1alphadriven endothelin 1 secretion by activating Nrf2/HO-1 and promoting the expression of prolyl hydroxylases 2/3 in human endothelial cells. Environ Toxicol. 2017;32(3):918-30.

Jiang CG, Li JB, Liu FR, Wu T, Yu M, Xu HM. Andrographolide inhibits the adhesion of gastric cancer cells to endothelial cells by blocking E-selectin expression. Anticancer Res. 2007;27(4B):2439-47.

Chao CY, Lii CK, Hsu YT, Lu CY, Liu KL, Li CC, Chen HW. Induction of heme oxygenase-1 and inhibition of TPA-induced matrix metalloproteinase- 9 expression by andrographolide in MCF-7 human breast cancer cells. Carcinogenesis. 2013;34(8):1843-51.

Luo W, Liu Y, Zhang J, Luo X, Lin C, Guo J. Andrographolide inhibits the activation of NF-kappaB and MMP-9 activity in H3255 lung cancer cells. Exp Ther Med. 2013;6(3):743-6.

Wu ZW, Xu HW, Dai GF, Liu MJ, Zhu LP, Wu J, Wang YN, Wu FJ, Zhao D, Gao MF, Nie SS, Han W, Song JH, Liu HM. Improved inhibitory activities against tumor-cell migration and invasion by 15-benzylidene substitution derivatives of andrographolide. Bioorg Med Chem Lett. 2013;23(23):6421-6.

Sheeja K, Guruvayoorappan C, Kuttan G. Antiangiogenic activity of Andrographis paniculata extract and andrographolide. Int Immunopharm. 2007;7:211-21.

Lin HH, Tsai CW, Chou FP, Wang CJ, Hsuan SW, Wang CK, Chen JH. Andrographolide down-regulates hypoxia-inducible factor-1alpha in human non-small cell lung cancer A549 cells. Toxicol Appl Pharmacol. 2011;250(3):336-45.

Li J, Zhang C, Jiang H, Cheng J. Andrographolide inhibits hypoxia-inducible factor-1 through phosphatidylinositol 3-kinase/AKT pathway and suppresses breast cancer growth. Onco Targets Ther. 2015;8:427-35.

Gong C, Xu C, Ji L, Wang Z. A novel semi-synthetic andrographolide analogue A5 inhibits tumor angiogenesis via blocking the VEGFR2-p38/ ERK1/2 signal pathway. Biosci Trends. 2013;7(5):230-6.

Kasemsuk S, Sirion U, Suksen K, Piyachaturawat P, Suksamrarn A, Saeeng R. 12-Amino-andrographolide analogues: synthesis and cytotoxic activity. Arch Pharm Res. 2013;36(12):1454-64.

Nateewattana J, Saeeng R, Kasemsook S, Suksen K, Dutta S, Jariyawat S, Chairoungdua A, Suksamrarn A, Piyachaturawat P. Inhibition of topoisomerase IIα activity and induction of apoptosis in mammalian cells by semi-synthetic andrographolide analogues. Invest New Drugs. 2013;31(2):320-32.

Sombut S, Bunthawong R, Sirion U, Kasemsuk T, Piyachaturawat P, Suksen K, Suksamrarn A, Saeeng R. Synthesis of 14-deoxy-11,12-didehydroandrographolide analogues as potential cytotoxic agents for cholangiocarcinoma. Bioorg Med Chem Lett. 2017;27(23):5139-43.

Arsakhant P, Sirion U, Chairoungdua A, Suksen K, Piyachaturawat P, Suksamrarn A, Saeeng R. Design and synthesis of C-12 dithiocarbamate andrographolide analogues as an anticancer agent. Bioorg Med Chem Lett. 2020;30(14):127263.

Bunthawong R, Sirion U, Chairoungdua A, Suksen K, Piyachaturawat P, Suksamrarn A, Saeeng R. Synthesis and cytotoxic activity of new 7-acetoxy-12-amino-14-deoxy andrographolide analogues. Bioorg Med Chem Lett. 2021;33:127741.