Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth

Rawangkan, Anchalee; Wongsirisin, Pattama; Namiki, Kozue; Iida, Keisuke; Kobayashi, Yasuhito; Shimizu, Yoshihiko; Fujiki, Hirota; Suganuma, Masami

doi:10.3390/molecules23082071

Cited by 109 publications

(77 citation statements)

References 31 publications

(49 reference statements)

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“…In particular, catechins can selectively kill cancer cells by promoting ROS generation over a critical threshold and by mobilization of endogenous chromatin-bound copper ions [30]. Among catechins, EGCG from green tea is one of the most studied, and it has been reported to be active against many types of cancer, including colorectal [31], lung [32], breast [33] and liver [34]. These effects basically arise from its abilities to promote pro-apoptotic effects, inhibit angiogenesis, regulate cellular metabolic pathways, and reduce inflammatory factors [28,35].…”

Section: Discussionmentioning

confidence: 99%

Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells

Chiaino

Micucci

Budriesi

et al. 2020

IJMS

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The research for innovative treatments against colon adenocarcinomas is still a great challenge. Acacia catechu Willd. heartwood extract (AC) has health-promoting qualities, especially at the gastrointestinal level. This study characterized AC for its catechins content and investigated the apoptosis-enhancing effect in human colorectal adenocarcinoma HT-29 cells, along with its ability to spare healthy tissue. MTT assay was used to describe the time course, concentration dependence and reversibility of AC-mediated cytotoxicity. Cell cycle analysis and AV-PI and DAPI-staining were performed to evaluate apoptosis, together with ROS formation, mitochondrial membrane potential (MMP) changes and caspase activities. Rat ileum and colon rings were tested for their viability and functionality to explore AC effects on healthy tissue. Quantitative analysis highlighted that AC was rich in (±)-catechin (31.5 ± 0.82 mg/g) and (−)-epicatechin (12.5 ± 0.42 mg/g). AC irreversibly decreased cell viability in a concentration-dependent, but not time-dependent fashion. Cytotoxicity was accompanied by increases in apoptotic cells and ROS, a reduction in MMP and increases in caspase-9 and 3 activities. AC did not affect rat ileum and colon rings' viability and functionality, suggesting a safe profile toward healthy tissue. The present findings outline the potential of AC for colon cancer treatment.3 of 17 at approximately the same content level was observed (Figure 1b). The latter was assumed as a marker of the epimerization as the consequence of the process applied in decoction preparation (thermal treatment). Analysis of decoction preparations stored during very long-term period (at least two years) at room temperature in the dark, did not show loss of (−)-EC and (+)-C, nor epimerization progression, thus suggesting very high chemical stability of the preparation. Int. J. Mol. Sci. 2020, 21, x FOR PEER REVIEW 3 of 17 period (at least two years) at room temperature in the dark, did not show loss of (−)-EC and (+)-C, nor epimerization progression, thus suggesting very high chemical stability of the preparation.

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Section: Discussionmentioning

confidence: 99%

Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells

Chiaino

Micucci

Budriesi

et al. 2020

IJMS

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“…In addition to anti-cancer effects, EGCG shows a significant inhibitory effect on interferon-γ (IFN-γ)-induced indoleamine 2,3-dioxygenase (IDO) expression, an enzyme that guides cancer to regulate immune response, in human colorectal cancer SW-837 cells [108], so this suggests that EGCG might be useful for chemoprevention and colorectal cancer treatment, and could be a potential agent for anti-tumor immunotherapy. EGCG is also found to be a potential immune checkpoint inhibitor, which down-regulates IFN-γ-induced B7 homolog 1 (B7-H1) levels, an immunoglobulin-like immune suppressive molecule, in human NSCLC A549 cells [109].…”

Section: Epigallocatechin Gallate (Egcg)mentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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“…EGCG has additionally shown synergistic activity with other anti-cancer treatments, such as tamoxifen (hormone therapy) and nonsteroidal anti-inflammatory drugs (NSAIDs, i.e., cyclooxygenase-2 (COX-2) inhibitors) [145]. EGCG and whole green tea extract also acted as immune checkpoint inhibitors by decreasing the expression of PDL-1 on alveolar adenocarcinoma cell lines and in in vivo murine lung cancer models [146]. It is known that EGCG affects signalling pathways involved in proliferation and apoptosis and is able to inhibit nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathways and other molecular targets involved in the progression of cancer [119,147].…”

Section: Egcgmentioning

confidence: 99%

Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells

Moody

Wilson

Jaworowski

et al. 2020

Cancers

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Cancer-related deaths are approaching 10 million each year. Survival statistics for some cancers, such as ovarian cancer, have remained unchanged for decades, with women diagnosed at stage III or IV having over 80% chance of a lethal cancer recurrence after standard first-line treatment (reductive surgery and chemotherapy). New treatments and adjunct therapies are needed. In ovarian cancer, as in other cancers, the immune response, particularly cytotoxic (CD8+) T cells are correlated with a decreased risk of recurrence. As well as completely new antigen targets resulting from DNA mutations (neo-antigens), these T cells recognize cancer-associated overexpressed, re-expressed or modified self-proteins. However, there is concern that activation of self-reactive responses may also promote off-target pathology. This review considers the complex interplay between cancer-reactive and self-reactive immune cells and discusses the potential uses for various leading immunomodulatory compounds, derived from plant-based sources, as a cancer therapy option or to modulate potential autoimmune pathology. Along with reviewing well-studied compounds such as curcumin (from turmeric), epigallocatechin gallate (EGCG, from green tea) and resveratrol (from grapes and certain berries), it is proposed that compounds from novel sources, for example, native Australian plants, will provide a useful source for the fine modulation of cancer immunity in patients.

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Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth

Cited by 109 publications

References 31 publications

Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells

Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells

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