Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models

Abstract

BackgroundChemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed.Methods/DesignThe study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification.ResultsPromising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO and AL), and anti-ulcer (CUR, ZO, and AL) activities.ConclusionPlants used in Thai traditional medicine for the treatment of various ailments may provide reservoirs of promising candidate chemotherapeutics for the treatment of CCA.

Synergistic effects of 5-aminolevulinic acid based photodynamic therapy and celecoxib via oxidative stress in human cholangiocarcinoma cells

“…The drugs, in a 50 µL volume, were directly injected into each tumor area. [26][27][28][29][30][31] At 4 hours after treatment, mice were irradiated with a fluence of 2 J/cm 2 . Tumor volumes and body weights were measured every 3-4 days from 2 weeks after PDT.…”

Autophagy-associated Targeting Pathways of Natural Products during Cancer Treatment

“…Curcumin has a wide range of biological functions, especially the anticancer activity. It can inhibit the proliferation of tumor cells, and induce the apoptosis of tumor cells including bladder cancer (Gao et al, 2012), pancreatic cancer (Plengsuriyakarn et al, 2012), prostate cancer (Zhou et al, 2014) and uterine cervix carcinoma (Odot et al, 2004). Curcumin also exhibits favorable synergistic performance both in thermotherapy and γ-ray therapy for cancers (Bansal et al, 2011).…”

Phytochemical importance of medicinal plants as potential sources of anticancer agents

“…Its major chemical constituent is curcumin and it exhibits numerous biological actions. The curcumin compound also exhibits antitumor potential via suppression of the various events involved in multiple steps of carcinogenesis such as transcription factor, NF-κB, AP-1, and STAT-3 and the ability to repress proinflammatory pathways of COX-2 and iNOS (Plengsuriyakarn et al, 2012).…”

“…In pancreatic cancer cell lines, it is known to inhibit the formation of blood capillaries (Kuete et al, 2011 (Ali and Bluden, 2003). Thymoquinone, a secondary metabolite of this plant, has cytotoxic effects as it induces apoptosis in tumor cells by suppressing NF-κB, Akt activation, and extracellular signal-regulated kinase signaling pathways; it also inhibits tumor angiogenesis (Plengsuriyakarn et al, 2012).…”