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Multidrug resistance (MDR) of cancer cells constitutes one of the main reasons for chemotherapy failure. The search for nontoxic modulators that reduce MDR is a task of great importance. An ability to enhance apoptosis of resistant cells would also be beneficial. In the present study, the MDR reversal and apoptosis-inducing potency of three flavonoids produced by Citrus plants, namely, naringenin (1a), aromadendrin (2), and tangeretin (3), and the methylated naringenin derivatives (1b, 1c), have been studied in sensitive (LoVo) and multidrug-resistant (LoVo/Dx) human colon adenocarcinoma cells. Cytotoxicity of methoxylated flavonoids was higher as compared to hydroxylated analogues. Only 3 turned out to inhibit P-glycoprotein, as demonstrated by a rhodamine 123 accumulation assay. It also increased doxorubicin accumulation in LoVo/Dx cells and enabled doxorubicin to enter cellular nuclei. In addition, 3 was found to be an effective MDR modulator in resistant cells by sensitizing them to doxorubicin. Tangeretin-induced caspase-3 activation and elevated surface phosphatidylserine exposure demonstrated its apoptosis-inducing activity in LoVo/Dx cells, while the other flavonoids evaluated were not active. Additionally, 3 was more toxic to resistant rather than to sensitive cancer cells. Its apoptosis-inducing activity was also higher in LoVo/Dx than in LoVo cells. It was concluded that the activity of 3 against multidrug-resistant cancer cells may be enhanced by its apoptosis-inducing activity.

Aphids (Hemiptera: Aphididae) are herbivorous insects which deprive plants of nutrients by feeding on the phloem sap and transmission of plant viruses. In the present study, the susceptibility of selected white-berried grapevine (Vitis spp.) cultivars "Aurora", "Bianca", "Muskat Letni" and "Solaris" to the black bean aphid (Aphis fabae Scop.) and the green peach aphid (Myzus persicae (Sulz.) was evaluated using the Electrical Penetration Graph (EPG) technique. The content of major flavonoids and stilbenoids in grapevine leaves and leaf anatomy parameters that might have affected aphid probing were also analyzed. Based on the success rate in reaching the phloem vessels and feeding on phloem sap, the studied grapevine cultivars can be assigned to various groups of susceptibility. Cultivars "Bianca" and "Muskalt Letni" are susceptible to A. fabae and M. persicae, respectively (aphids reach phloem phase and show short bouts of sap ingestion); "Muskat Letni" shows low susceptibility to A. fabae, while "Aurora" and "Bianca" to M. persicae (only 50% aphids reach phloem phase and no sap ingestion occurs); "Solaris" is resistant to A. fabae and M. persicae (no phloem phase present). Anatomical structure of leaves was similar in all cultivars and no mechanical barriers for aphid probing were observed. However, the content of individual flavonoids and silbenoids differed among cultivars. We hypothesize that the high content of piceid in the leaves of "Solaris" may be responsible for the rejection of this cultivar by both aphid species. The study demonstrated that the risk of the direct damage due to A. fabae and M. persicae feeding on grapevines is low. However, considering the intense aphid probing activity within leaf epidermis and mesophyll, A. fabae and M. persicae may pose a serious threat as vectors of non-persistent and semi-persistent viruses to white-berried grapevines. [ABSTRACT FROM AUTHOR]

The peach-potato aphid Myzus persicae (Sulzer) and the black bean aphid Aphis fabae Scopoli are polyphagous and cosmopolitan hemipterans, therefore they can infest grapevines in all areas of cultivation. Electrical Penetration Graph (EPG) technique was applied to monitor the probing behavior of A. fabae and M. persicae on Vitis amurensis Rupr., Vitis riparia Michaux, and Vitis vinifera L. The content of major flavonoids and stilbenoids in grapevine leaves and epidermal thickness, distance between abaxial leaf surface and phloem, and the simulated shortest pathway from epidermis to phloem that might have affected aphid probing were also analyzed. Aphid probing was limited mainly to non-vascular tissues on the three studied grapevine species. Phloem phase occurred in 32%, 14%, and 6% of A. fabae and in 76%, 39%, and 74% of M. persicae on V. amurensis, V. riparia and V. vinifera, respectively. Phloem phase consisted of only salivation into sieve elements and lasted less than 2.5 minutes on average in all aphids. The time to reach the first phloem phase on grapevines was 5.0 hours in A. fabae and 2.6–3.6 hours in M. persicae. Of the analyzed flavonoids, catechin, epicatechin, and quercetin occurred in all grapevine species, while rutin – in V. amurensis and V. riparia and isorhamnetin only in V. amurensis. Of the analyzed stilbenoids, piceid occurred in all grapevines, resveratrol in V. amurensis and V. vinifera, and ε-viniferin only in V. vinifera. Aphid behavior demonstrated that V. amurensis, V. riparia and V. vinifera are not attractive host plants to A. fabae and M. persicae. It is likely that the content of flavonoids and stilbenoids contributes to the limited susceptibility of the three grapevine species to A. fabae and M. persicae, while the observed slight differences in the anatomical structure of the leaves seem not significant in this context. [ABSTRACT FROM AUTHOR]