Induction of apoptosis in cholangiocarcinoma by an andrographolide analogue is mediated through topoisomerase II alpha inhibition

Nateewattana, Jintapat; Dutta, Suman; Reabroi, Somrudee; Saeeng, Rungnapha; Kasemsook, Sakkasem; Chairoungdua, Arthit; Weerachayaphorn, Jittima; Wongkham, Sopit; Piyachaturawat, Pawinee

doi:10.1016/j.ejphar.2013.12.002

Cited by 32 publications

(11 citation statements)

References 26 publications

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“…Andrographolide also induces cell cycle arrest and apoptosis of cancer cells by inhibiting phosphoinositide 3-kinase/protein kinase B, mitogen-activated protein kinase and other tumor growth pathways, depending on the type of treated cells (15)(16)(17)(18). Andrographolide triggers intrinsic and extrinsic apoptotic pathways in different cancer cells via mechanisms involving activation of p53, reactive oxygen species (ROS) and topoisomerase II (17,19,20). Furthermore, andrographolide demonstrated a potent anticancer effect when it was applied in combination with other anticancer agents, including cisplatin and doxorubicin (21,22).…”

Section: Introductionmentioning

confidence: 99%

Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells

et al. 2017

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Abstract. Andrographolide, a natural compound isolated from Andrographis paniculata, has been reported to possess antitumor activity. In the present study, the effect of andrographolide in human gastric cancer (GC) cells was investigated. Andrographolide induced cell death with apoptotic and non-apoptotic features. At a low concentration, andrographolide potentiated apoptosis and reduction of clonogenicity triggered by recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL). Exposure of GC cells to andrographolide altered the expression level of several growth-inhibiting and apoptosis-regulating proteins, including death receptors. It was demonstrated that activity of the TRAIL-R2 (DR5) pathway was critical in the development of andrographolide-mediated rhTRAIL sensitization, since its inhibition significantly reduced the extent of apoptosis induced by the combination of rhTRAIL and andrographolide. In addition, andrographolide increased reactive oxygen species (ROS) generation in a dose-dependent manner. N-acetyl cysteine prevented andrographolide-mediated DR5 induction and the apoptotic effect induced by the combination of rhTRAIL and andrographolide. Collectively, the present study demonstrated that andrographolide enhances TRAIL-induced apoptosis through induction of DR5 expression. This effect appears to involve ROS generation in GCs.

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Section: Introductionmentioning

confidence: 99%

Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells

et al. 2017

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“…It also suppressed the expression of DNA topoisomerase II α. This is found capable for induction of apoptosis in primary malignant tumor of bile duct epithelial cells(67).…”

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confidence: 96%

Andrographolide and analogues in cancer prevention

Mishra¹

2015

Front Biosci

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Andrographis paniculata is a medicinal plant traditionally used for treatment of cough and cold, fever, laryngitis, and several infectious diseases. Extracts of A. paniculata have shown versatile potency against various diseases including cancer. The active biomolecules of A. paniculata mainly are lactone and diterpene. Andrographolide and analogues have been widely used for prevention of different diseases. Andrographolides have shown potent antiinflammatory and anticancer activities. It showed potentials as chemopreventive agents by suppressing growth of cancer cells by inhibiting NF-kappaB, PI3K/AKT and other kinase pathways and by inducing apoptosis. Andrographolide induced both intrinsic and extrinsic apoptosis pathway in different cancer cells via expression of different anti-apoptotic protein like Bax, p53, and activated caspases. Andrographolide was successfully used as an antineoplastic drug in cancer chemotherapy. Andrographolide inhibited the growth of human breast, prostate, and hepatoma tumors. Andrographolide and analogues need to be subjected to further clinical and biomedical studies in cancer chemoprevention. Andrographolide could be potent anticancer agent when used in combination with other chemotherapeutic agents.

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“…Our observations are in line with previous studies which indicated that AP 1 induced cell cycle arrest at the G0/G1 or G2/M phase in various cancer cell lines, for example, hepatoma cells (HepG2 and Hep3B) [16,28], colorectal carcinoma Lovo cells [29], prostate cancer PC-3 cells [30], acute myeloid leukemic HL-60 cells [31], and lung adenocarcinoma CL1-5 cells [32]. Furthermore, a recent study demonstrated that the AP 1 analogue, which was modified from the parent compound by adding an epoxide moiety at the core structure C-17 and a silicon-based molecule, tert-butyldiphenylsilyl, at the C-19 side chain, induced adenosquamous cholangiocarcinoma KKU-M213 cell cycle arrest at the sub-G0 and G2/M phases [22]. Our results also indicated that A. paniculata extract induced intrahepatic cholangiocarcinoma cell apoptosis.…”

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confidence: 99%

Andrographis paniculata Extracts and Major Constituent Diterpenoids Inhibit Growth of Intrahepatic Cholangiocarcinoma Cells by Inducing Cell Cycle Arrest and Apoptosis

et al. 2014

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Andrographis paniculata is an important herbal medicine widely used in several Asian countries for the treatment of various diseases due to its broad range of pharmacological activities. The present study reports that A. paniculata extracts potently inhibit the growth of liver (HepG2 and SK-Hep1) and bile duct (HuCCA-1 and RMCCA-1) cancer cells. A. paniculata extracts with different contents of major diterpenoids, including andrographolide, 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, and 14-deoxyandrographolide, exhibited a different potency of growth inhibition. The ethanolic extract of A. paniculata at the first true leaf stage, which contained a high amount of 14-deoxyandrographolide but a low amount of andrographolide, showed a cytotoxic effect to cancer cells about 4 times higher than the water extract of A. paniculata at the mature leaf stage, which contained a high amount of andrographolide but a low amount of 14-deoxyandrographolide. Andrographolide, not 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, or 14-deoxyandrographolide, possessed potent cytotoxic activity against the growth of liver and bile duct cancer cells. The cytotoxic effect of the water extract of A. paniculata at the mature leaf stage could be explained by the present amount of andrographolide, while the cytotoxic effect of the ethanolic extract of A. paniculata at the first true leaf stage could not. HuCCA-1 cells showed more sensitivity to A. paniculata extracts and andrographolide than RMCCA-1 cells. Furthermore, the ethanolic extract of A. paniculata at the first true leaf stage increased cell cycle arrest at the G0/G1 and G2/M phases, and induced apoptosis in both HuCCA-1 and RMCCA-1 cells. The expressions of cyclin-D1, Bcl-2, and the inactive proenzyme form of caspase-3 were reduced by the ethanolic extract of A. paniculata in the first true leaf stage treatment, while a proapoptotic protein Bax was increased. The cleavage of poly (ADP-ribose) polymerase was also found in the ethanolic extract of A. paniculata in the first true leaf stage treatment. This study suggests that A. paniculata could be a promising herbal plant for the alternative treatment of intrahepatic cholangiocarcinoma.

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Induction of apoptosis in cholangiocarcinoma by an andrographolide analogue is mediated through topoisomerase II alpha inhibition

Cited by 32 publications

References 26 publications

Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells

Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells

Andrographolide and analogues in cancer prevention

Andrographis paniculata Extracts and Major Constituent Diterpenoids Inhibit Growth of Intrahepatic Cholangiocarcinoma Cells by Inducing Cell Cycle Arrest and Apoptosis

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