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Dehydrocrenatidine Induces Liver Cancer Cell Apoptosis by Suppressing JNK-Mediated Signaling

Bharath Kumar Velmurugan1, Ming-Ju Hsieh2,3,4, Chia-Chieh Lin2

  • 1Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City 756000, Vietnam.

Pharmaceuticals (Basel, Switzerland)
|April 23, 2022
PubMed

Insights

Dehydrocrenatidine, a plant alkaloid, effectively inhibits liver cancer cell growth by halting cell division and triggering programmed cell death (apoptosis). This research highlights its potential as a novel therapeutic agent for liver cancer treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Liver cancer presents a significant global health challenge with poor patient outcomes due to aggressive disease characteristics and frequent recurrence.
  • Current therapeutic strategies for liver cancer face limitations in efficacy, necessitating the exploration of novel treatment options.

Purpose of the Study:

  • To investigate the anticancer potential of dehydrocrenatidine, a plant-derived alkaloid, against human liver cancer cells.
  • To elucidate the mechanisms underlying dehydrocrenatidine's anti-proliferative effects in liver cancer.

Main Methods:

  • Human liver cancer cells were treated with dehydrocrenatidine.
  • Cell viability, cell cycle progression, and apoptosis-related protein expression were analyzed.
  • Western blotting was used to assess the activation of intrinsic and extrinsic apoptotic pathways and upstream signaling molecules.

Main Results:

  • Dehydrocrenatidine significantly reduced liver cancer cell viability.
  • The compound induced cell cycle arrest at the G2/M phase.
  • Dehydrocrenatidine activated both mitochondria-mediated (intrinsic) and death receptor-mediated (extrinsic) apoptotic pathways, evidenced by increased Bax, Bim, FAS, DR5, and FADD expression, and enhanced cleavage of PARP and caspases 3, 8, and 9.
  • Suppression of JNK1/2 phosphorylation was observed, indicating its role in dehydrocrenatidine-induced apoptosis.

Conclusions:

  • Dehydrocrenatidine exhibits potent anticancer activity against human liver cancer cells.
  • The mechanism involves cell cycle arrest and induction of apoptosis through both intrinsic and extrinsic pathways, modulated by JNK signaling.
  • Dehydrocrenatidine represents a promising candidate for clinical development as a novel therapeutic agent for liver cancer.
Keywords:
JNKapoptosisdehydrocrenatidineliver

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