Photoactivation of pheophorbide a induces a mitochondrial-mediated apoptosis in Jurkat leukaemia cells

Lee, Won Young; Lim, Dae Seog; Ko, Si Hwan; Park, Young Jae; Ryu, Kang Sun; Ahn, Mi Young; Kim, Yong Rok; Lee, Dai Woon; Cho, Chang Whan

doi:10.1016/j.jphotobiol.2004.05.005

Cited by 47 publications

(32 citation statements)

References 32 publications

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“…PDT was reported to inhibit cancers through different cell death pathways and its effectiveness is dependent on the types of cancer cell lines and photosensitizers (Buytaert et al, 2007;Zuluaga and Lange, 2008). Previous studies on the potential of Pa as a photosensitizer have suggested that Pa is effective to inhibit cancer growth by the induction of apoptosis (Inanami et al, 1999;Hajri et al, 1999;Hajri et al, 2002;Lee et al, 2004;Lim et al, 2004;Tang et al, 2006;Li et al, 2007;Radestock et al, 2007;Kishino et al, 2008;Rapozzi et al, 2009;Tang et al, in press-a,b). We speculated that the apoptosis is a general anti-tumor mechanism of Pa-PDT on human cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Pa has been commercial available as it can be purified from a number of traditional medicine sources such as Scutellaria barbata, Psychotria acuminata, as well as silkworm excreta (Glinski et al, 1995;Lim et al, 2002;Chan et al, 2006). Previous studies have suggested that the therapeutic potential of Pa-mediated photodynamic therapy (Pa-PDT) on leukaemia, pigmented melanoma, colonic cancer, hepatoma and uterine carcinosarcoma (Hajri et al, 2002;Lee et al, 2004;Lim et al, 2004;Tang et al, 2006;Li et al, 2007;Tang et al, in press-a).…”

Section: Introductionmentioning

confidence: 99%

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Photo-activated pheophorbide-a, an active component of Scutellaria barbata, enhances apoptosis via the suppression of ERK-mediated autophagy in the estrogen receptor-negative human breast adenocarcinoma cells MDA-MB-231

Bui-Xuan

Tang

Wong

et al. 2010

Journal of Ethnopharmacology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Photo-activated pheophorbide-a, an active component of Scutellaria barbata, enhances apoptosis via the suppression of ERK-mediated autophagy in the estrogen receptor-negative human breast adenocarcinoma cells MDA-MB-231

Bui-Xuan

Tang

Wong

et al. 2010

Journal of Ethnopharmacology

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“…After sunrise, the photodynamic action will start. Photodynamic effects of chlorophyll and its derivates (pheophytin and conjugates) are also of interest, e.g., in photodynamic therapy research (Lee et al 2004;Kessel and Smith 1989). By means of fluorescence techniques and biochemical methods, it was found that chlorophyllin induces apoptosis, necrosis, and expression of heat shock proteins in Chaoborus larvae (Wohllebe and Grimm, manuscript in preparation).…”

Section: Discussionmentioning

confidence: 99%

Photodynamic control of human pathogenic parasites in aquatic ecosystems using chlorophyllin and pheophorbid as photodynamic substances

Wohllebe

Richter

et al. 2008

Parasitol Res

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When used at low concentrations and added to the water body, water-soluble chlorophyllin (resulting from chlorophyll after removal of the phytol) and pheophorbid (produced from chlorophyllin by acidification) are able to kill mosquito larvae and other small animals within a few hours under exposure of solar radiation. Under laboratory conditions, the use of chlorophyllin/pheophorbid as photodynamic substances for pest control in water bodies promises to be not only effective and ecologically beneficial but also cheap. The LD50 (50% of mortality in the tested organisms) value in Culex sp. larvae was about 6.88 mg/l, in Chaoborus sp. larvae about 24.18 mg/l, and in Daphnia 0.55 mg/l. The LD50 values determined for pheophorbid were 8.44 mg/l in Culex, 1.05 mg/l in Chaoborus, and 0.45 mg/l in Daphnia, respectively. In some cases, chlorophyllin and pheophorbid were also found to be (less) active in darkness. The results presented in this paper show that chlorophyllin is about a factor of 100 more effective than methylene blue or hematoporphyrine, which were tested earlier for the same purpose. It is also much cheaper and, as a substance found in every green plant, it is 100% biodegradable.

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“…Similar to photofrin, Pba induces apoptosis and necrosis in pancreatic carcinoma, leukemia, and hepatocellular carcinoma cells [13]–[15]. In uterine carcinoma cells, the underlying mechanism of apoptosis is Pba accumulation in the mitochondria, which leads to the generation of ROS and release of cytochrome c [16], [17]. Similarly, Pba causes mitochondria-dependent apoptosis in breast carcinoma MCF-7 cells [18].…”

Section: Introductionmentioning

confidence: 99%

The Sensitivity of Cancer Cells to Pheophorbide a-Based Photodynamic Therapy Is Enhanced by NRF2 Silencing

et al. 2014

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Photodynamic therapy (PDT) has emerged as an effective treatment for various solid tumors. The transcription factor NRF2 is known to protect against oxidative and electrophilic stress; however, its constitutive activity in cancer confers resistance to anti-cancer drugs. In the present study, we investigated NRF2 signaling as a potential molecular determinant of pheophorbide a (Pba)-based PDT by using NRF2-knockdown breast carcinoma MDA-MB-231 cells. Cells with stable NRF2 knockdown showed enhanced cytotoxicity and apoptotic/necrotic cell death following PDT along with increased levels of singlet oxygen and reactive oxygen species (ROS). A confocal microscopic visualization of fluorogenic Pba demonstrated that NRF2-knockdown cells accumulate more Pba than control cells. A subsequent analysis of the expression of membrane drug transporters showed that the basal expression of BCRP is NRF2-dependent. Among measured drug transporters, the basal expression of breast cancer resistance protein (BCRP; ABCG2) was only diminished by NRF2-knockdown. Furthermore, after incubation with the BCRP specific inhibitor, differential cellular Pba accumulation and ROS in two cell lines were abolished. In addition, NRF2-knockdown cells express low level of peroxiredoxin 3 compared to the control, which implies that diminished mitochondrial ROS defense system can be contributing to PDT sensitization. The role of the NRF2-BCRP pathway in Pba-PDT response was further confirmed in colon carcinoma HT29 cells. Specifically, NRF2 knockdown resulted in enhanced cell death and increased singlet oxygen and ROS levels following PDT through the diminished expression of BCRP. Similarly, PDT-induced ROS generation was substantially increased by treatment with NRF2 shRNA in breast carcinoma MCF-7 cells, colon carcinoma HCT116 cells, renal carcinoma A498 cells, and glioblastoma A172 cells. Taken together, these results indicate that the manipulation of NRF2 can enhance Pba-PDT sensitivity in multiple cancer cells.

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Photoactivation of pheophorbide a induces a mitochondrial-mediated apoptosis in Jurkat leukaemia cells

Cited by 47 publications

References 32 publications

Photo-activated pheophorbide-a, an active component of Scutellaria barbata, enhances apoptosis via the suppression of ERK-mediated autophagy in the estrogen receptor-negative human breast adenocarcinoma cells MDA-MB-231

Photo-activated pheophorbide-a, an active component of Scutellaria barbata, enhances apoptosis via the suppression of ERK-mediated autophagy in the estrogen receptor-negative human breast adenocarcinoma cells MDA-MB-231

Photodynamic control of human pathogenic parasites in aquatic ecosystems using chlorophyllin and pheophorbid as photodynamic substances

The Sensitivity of Cancer Cells to Pheophorbide a-Based Photodynamic Therapy Is Enhanced by NRF2 Silencing

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