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6-Shogaol enhances the anticancer effect of 5-fluorouracil, oxaliplatin, and irinotecan via increase of apoptosis and autophagy in colon cancer cells in hypoxic/aglycemic conditions.

ABSTRACT: BACKGROUND:The development and growth of colorectal cancer based on constitutive activation of numerous signaling pathways that stimulate proliferation and metastasis. Plant-derived agents excel by targeting multiple aspects of tumor progression. Previous investigations have shown that ginger derivatives- shogaols possess anti-cancer and anti-inflammatory effects. In the present study, we have examined the anti-cancer effects of 6-shogaol alongside with the most widely used chemotherapeutic agents/regimens in the tumor-like microenvironment conditions. METHODS:Cytotoxicity on two colon cancer cell lines (SW480 and SW620) was measured by MTT test. Apoptosisassay, immunocytochemical and Western blotting analysis for autophagy and apoptosis detection were performed. RESULTS:Here, we report that 6-shogaol by itself or in combination with chemotherapeutic agents/regimens exerted a cytotoxic effect on CRC cells. Cell death might be linked with the activation of autophagy and apoptosis-related pathways. In the tumor-like microenvironment, which is characterized by hypoxia and glucose starvation, 6-shogaol with chemotherapeutics is significantly more potent than conventional chemotherapy alone. CONCLUSIONS:Collectively, our data suggest that the addition of 6-shogaol to established chemotherapeutic regimens could potentially be a remarkable therapeutic strategy for colorectal cancer.

SUBMITTER: Wozniak M

PROVIDER: S-EPMC7216385 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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6-Shogaol enhances the anticancer effect of 5-fluorouracil, oxaliplatin, and irinotecan via increase of apoptosis and autophagy in colon cancer cells in hypoxic/aglycemic conditions.

Woźniak Marta M Makuch Sebastian S Winograd Kinga K Wiśniewski Jerzy J Ziółkowski Piotr P Agrawal Siddarth S

BMC complementary medicine and therapies 20200511 1

<h4>Background</h4>The development and growth of colorectal cancer based on constitutive activation of numerous signaling pathways that stimulate proliferation and metastasis. Plant-derived agents excel by targeting multiple aspects of tumor progression. Previous investigations have shown that ginger derivatives- shogaols possess anti-cancer and anti-inflammatory effects. In the present study, we have examined the anti-cancer effects of 6-shogaol alongside with the most widely used chemotherapeu ...[more]

PMID: 32393373

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Project description:BackgroundUp-front surgery followed by postoperative chemotherapy remains the standard paradigm for the treatment of patients with resectable pancreatic cancer. However, the risk for positive surgical margins, the poor recovery after surgery that often impairs postoperative treatment, and the common metastatic relapse limit the overall clinical outcomes achieved with this strategy. Polychemotherapeutic combinations are valid options for postoperative treatment in patients with good performance status. liposomal irinotecan (Nal-IRI) is a novel nanoliposome formulation of irinotecan that accumulates in tumor-associated macrophages improving the therapeutic index of irinotecan and has been approved for the treatment of patients with metastatic pancreatic cancer after progression under gemcitabine-based therapy. Thus, it remains of the outmost urgency to investigate introduction of the most novel agents, such as nal-IRI, in perioperative approaches aimed at increasing the long-term effectiveness of surgery.MethodsThe nITRO trial is a phase II, single-arm, open-label study to assess the safety and the activity of nal-IRI with fluorouracil/leucovorin (5-FU/LV) and oxaliplatin in the perioperative treatment of patients with resectable pancreatic cancer. The primary tumor must be resectable with no involvement of the major arteries and no involvement or <180° interface between tumor and vessel wall of the major veins. A total of 72 patients will be enrolled to receive a perioperative treatment of three cycles before and three cycles after surgical resection with nal-IRI 50?mg/m2, oxaliplatin 60?mg/m2, leucovorin 200?mg/m2, and 5-fluorouracil 2400?mg/m2, days 1 and 15 of a 28-day cycle. The primary objective is to improve from 40% to 55% the proportion of patients achieving R0 resection after preoperative treatment.DiscussionThe nITRO trial will contribute to strengthen the clinical evidence supporting perioperative strategies in resectable pancreatic cancer patients. Moreover, this study represents a unique opportunity for translational analyses aimed to identify novel immune-related prognostic and predictive factors in this setting.Trial registrationClinicaltrial.gov: NCT03528785. Trial registration data: 1 January 2018Protocol number: CRC 2017_01EudraCT Number: 2017-000345-46.

Dataset Information

6-Shogaol enhances the anticancer effect of 5-fluorouracil, oxaliplatin, and irinotecan via increase of apoptosis and autophagy in colon cancer cells in hypoxic/aglycemic conditions.

Publications

6-Shogaol enhances the anticancer effect of 5-fluorouracil, oxaliplatin, and irinotecan via increase of apoptosis and autophagy in colon cancer cells in hypoxic/aglycemic conditions.

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